DIFFERENTIAL EXPRESSION OF TRKC CATALYTIC AND NONCATALYTIC ISOFORMS SUGGESTS THAT THEY ACT INDEPENDENTLY OR IN ASSOCIATION

Members of the trh gene family encode neurotrophin receptors. The trkC locus encodes multiple neurotrophin-3 catalytic and noncatalytic rece ptor isoforms. We report the molecular cloning and characterization of mouse cDNAs encoding two noncatalytic TrkC receptors: novel isoforms designated as TrkC NC1 and TrkC NC2, the mouse homologue of the TrkC t runcated form previously identified in rat (Tsoulfas et al. [1993] Neu ron 10:975-990; Valenzuela et al. [1993] Neuron 10:963-974). We extens ively analyzed the transcription pattern of these two noncatalytic iso forms and that of the catalytic isoforms by Northern blotting and in s itu hybridization. We did not detect trkC NCI transcripts in embryos, but we found that trkC NC1 expression is restricted to specific areas in adult brain. In contrast, trkC NC2 transcripts are readily detected early during embryogenesis and are expressed predominantly in adult b rain and gonads. We also provide the first evidence for the existence of TrkC NC2 protein by using polyclonal antibodies that specifically r ecognize this isoform. By using in situ hybridization, we show for the first time that trkC NC2 transcripts are found in differentiating fie lds of maturing neurons and in mature neurons of laminar structures of adult brain. We also report a similarity of localization between trkC NC2 transcripts and markers of oligodendrocyte progenitors in the emb ryonic spinal cord. Furthermore, our results also show that trkC NC2 a nd trkC catalytic transcripts could be either codistributed (in the ce ntral and peripheral nervous system) or independently expressed, espec ially outside the nervous system. These results suggest that the TrkC NC2 isoform acts either independently or in association with its catal ytic counterpart. Finally, we show that TrkC NC2 is expressed in dendr ites of pyramidal neurons of hippocampus and cerebral cortex. We propo se that this receptor is involved in proliferation of oligodendrocyte progenitors, neuronal differentiation, and synaptic plasticity and tha t it may also play a fundamental role in mediating neurotrophin-3 effe cts outside the nervous system. (C) 1998 Wiley-Liss, Inc.